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Neuropathological and histochemical changes in a multiple mitochondrial DNA deletion disorder

Lookup NU author(s): Dr David Cottrell, Dr Margaret Johnson, Professor Patrick Chinnery, Emeritus Professor Doug Turnbull


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The identification of cytochrome c oxidase (COX)-deficient/succinate dehydrogenase (SDH)- positive cells using sequential histochemistry has proved important in the identification of cells with high mitochondrial. DNA (mtDNA) mutant load. We demonstrate large numbers of COX-deficient/SDH- positive neurons in a mosaic pattern throughout the CNS of a patient with a multiple mtDNA deletion disorder. This patient had prominent central and peripheral nervous system involvement with marked cerebellar ataxia, a parkinsonian extra-pyramidal movement disorder, external ophthalmoplegia, dysphagia, and a severe peripheral neuropathy. There was degeneration of myelin tracts in the cerebellum and dorsal spinal columns, diffuse astrocytosis, and selective neuronal degeneration particularly in the midbrain and cerebral microvacuolation. The proportional distribution of the COX-deficient neurons did not always correlate directly with the degree of neuropathological damage with regions of high neuronal loss having relatively low proportions of these cells. Other clinically affected CNS regions have high levels of COX-deficient neurons without significant cell loss. The role of these COX-deficient neurons in causing neuronal degeneration and clinical symptoms is discussed.

Publication metadata

Author(s): Cottrell DA, Ince PG, Blakely EL, Johnson MA, Chinnery PF, Hanna M, Turnbull DM

Publication type: Review

Publication status: Published

Journal: Journal of Neuropathology and Experimental Neurology

Year: 2000

Volume: 59

Issue: 7

Pages: 621-627

Print publication date: 01/07/2000

ISSN (print): 0022-3069

ISSN (electronic): 1554-6578

PubMed id: 10901234